Whether or not severe febrile seizures in infancy cause hippocampal injury and subsequent medial temporal sclerosis is an often debated question in epilepsy. Recent magnetic resonance imaging (MRI) of infants suffering from febrile seizures has provided preliminary evidence that abnormally increased T2 signal intensity can be seen in the hippocampi of infants following prolonged and focal febrile seizures. Follow-up MRIs in a few of these infants have confirmed that medial temporal sclerosis can develop following these acute MRI signal changes. In this article, we review the hypotheses and MRI evidence relating to hippocampal injury during prolonged febrile seizures and the later development of medial temporal sclerosis.